This project is based on the hypothesis that NK cells, activated either in vivo or ex vivo (and subsequently transferred back into the recipient), might constitute an effective therapy of disseminated cancer. The applicant will therefore test and compare the anti-neoplastic effect of activated NK cells in rat models of disseminated breast cancer at different stages of progression (i.e., early, late, and dormant metastases). This will be done by: 1) measuring the accumulation of both endogenous NK cells and adoptively transferred IL-2-activated NK (A-NK) cells into early and late MADB106 mammary carcinoma metastases, and the extent of NK cell attack and destruction of such lesions; 2) determining the ability of endogenous NK cells and adoptively transferred A-NK cells to localize into dormant versus active metastases of the EMS-86 mammary carcinoma, and analyzing whether activation of endogenous NK cells and/or the adoptive transfer of A-NK cells during the dormant state of metastatic breast cancer disease can prevent the recurrence of metastatic growth. Furthermore, studies will be carried out to evaluate both the adhesion molecules involved in localization of endogenous NK cells and adoptively transferred A-NK cells into metastases and the mechanisms behind the anti-neoplastic effects mediated by NK/A-NK cells. The investigator believes that these studies will provide information and insights that might be translatable to new clinical strategies for improving treatment of women with metastatic breast cancer and identify the size and/or stage of metastases most likely to respond to immunotherapeutic approaches based on NK cells.